The Exposure of Breast Cancer Cells to Fulvestrant and Tamoxifen Modulates Cell Migration Differently

Abstract

There is no doubt that there are increased benefits of hormonal therapy to breast cancer patients; however, current evidence suggests that estrogen receptor (ER) blockage using antiestrogens is associated with a small induction of invasiveness in vitro. The mechanism by which epithelial tumor cells escape from the primary tumor and colonize to a distant site is not entirely understood. This study investigates the effect of two selective antagonists of the ER, Fulvestrant (Fulv) and Tamoxifen (Tam), on the invasive ability of breast cancer cells. We found that 17β-estradiol (E2) demonstrated a protective role regarding cell migration and invasion. Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression. Furthermore, both tested agents increased expression of matrix metalloproteinases (MMPs) and enhanced invasive potential of breast cancer cells. These changes were in line with focal adhesion kinase (FAK) rearrangement. Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events. Although Fulv caused a less aggressive result compared to Tam, the benefits of hormonal therapy concerning invasion and metastasis yet remain to be investigated.

Inhibition of FASN and ERα signalling during hyperglycaemia-induced matrix-specific EMT promotes breast cancer cell invasion via a caveolin-1-dependent mechanism

“…However, our findings add to the growing debate over the clinical benefits of these therapeutic drugs. In agreement with our study, Borley and co-workers recently showed that fulvestrant and tamoxifen promote an invasive phenotype in E-cadherin deficient MCF-7 cells by activating Src kinase [ 32 ] and others have found that these endocrine agents modulate cell invasion via distinct mechanisms [ 33 ]. Furthermore, tamoxifen treatment has been reported to induce the expression of matrix metalloproteinases (MMPs) [ 34 ], the well-known ECM-degrading enzymes that participate in tumour invasion [ 35 ].…”

Self‐Assembled Peptide‐Based Biocomposites for Near‐Infrared Light Triggered Drug Release to Tumor Cells

“…Fulvestrant has been known to affect cell proliferation but has little to no effect on cell migration due to its ability to disrupt the dimerization process of the estrogen receptors. [71] The ability of irradiated gold-nanorod-bound assemblies to interact with actin filaments, which are crucial in cell invasion, supports our finding that the irradiated DDV2s were more successful at preventing cell invasion. Thus, gold-nanorod-bound FLS DDVs could play a pivotal role in reducing cell invasion and metastasis.…”

“…[25] Furthermore, fulvestrant is hydrophobic and thus can bind efficiently to the assemblies and improve entrapment. [26,27] For DDV2, the self-assembled FLS nanoassemblies were first attached with gold-nanorods (10 nm in diameter) through cysteine-thiol chemistry in order to facilitate a photo-triggered drug release before encapsulating DDV2 with fulvestrant. Drug release, cytotoxicity, cell invasion studies, and impacts on actin cytoskeleton were examined before and after irradiation with 785 nm near-infrared laser for DDV2.…”

Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats

“…Tamoxifen is SERM acting on the β -estradiol estrogen receptors (ER) [ 14 , 15 ]. It has clinical therapeutic uses in human breast cancer treatment.…”